For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
64
views
37
references
 Top references
cited by
48
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      32
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          BLyS expression by GC follicular T cells is required for the efficient selection of high-affinity GC B cells.

          Abstract

          We have assessed the role of B lymphocyte stimulator (BLyS) and its receptors in the germinal center (GC) reaction and affinity maturation. Despite ample BLyS retention on B cells in follicular (FO) regions, the GC microenvironment lacks substantial BLyS. This reflects IL-21–mediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) on GC B cells, thus limiting their capacity for BLyS binding and retention. Within the GC, FO helper T cells (T FH cells) provide a local source of BLyS. Whereas T cell–derived BLyS is dispensable for normal GC cellularity and somatic hypermutation, it is required for the efficient selection of high affinity GC B cell clones. These findings suggest that during affinity maturation, high affinity clones rely on T FH-derived BLyS for their persistence.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells

          Brian O'Connor, Vanitha Raman, Loren D. Erickson … (2004)
          Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by interleukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this α-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival in vitro and in vivo. Heightened expression of B cell maturation antigen (BCMA), and lowered expression of transmembrane activator and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B cells suggests a vital role of BCMA in PC survival. Affirmation of the importance of BCMA in PC survival was provided by studies in BCMA−/− mice in which the survival of long-lived bone marrow PCs was impaired compared with wild-type controls. These findings offer new insights into the molecular basis for the long-term survival of PCs.
          Article 0 comments Cited 282 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth

            Pascal Schneider, Fabienne Mackay, Véronique Rochat-Steiner … (1999)
            Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M–stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center–like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.
            Article 0 comments Cited 274 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells

              Kim L. Good-Jacobson, Courtney Szumilas, Lieping Chen … (2010)
              Memory B and plasma cells (PCs) are generated in the germinal center (GC). As PD-1 is highly expressed in T follicular helper cells (TFH), we investigated the role of PD-1 signaling in the humoral response. We found that PD-L1 and PD-L2 are upregulated on GC B cells. Pdcd1lg2 −/− , CD274 −/− Pdcd1lg2 −/− and Pdcd1 −/− mice had reduced numbers of long-lived PCs. The mechanism involved increased GC cell death and decreased TFH cytokine production in the absence of PD-1; the effect was selective, as remaining PCs had higher affinity. PD-1 expression on T cells and PD-L2 expression on B cells controlled TFH and PC numbers. Thus, PD-1 regulates selection and survival in the GC, impacting the quantity and quality of long-lived PCs.
              Article 0 comments Cited 234 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): J Exp Med
                Journal ID (iso-abbrev): J. Exp. Med
                Journal ID (hwp): jem
                Title: The Journal of Experimental Medicine
                Publisher: The Rockefeller University Press
                ISSN (Print): 0022-1007
                ISSN (Electronic): 1540-9538
                Publication date (Print): 13 January 2014
                Volume: 211
                Issue: 1
                Pages: 45-56
                Affiliations
                [1 ]Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104
                [2 ]School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104
                [3 ]Human Genome Sciences, Inc., Rockville, MD 20850
                [4 ]Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892
                [5 ]Division of Rheumatology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033
                Author notes
                CORRESPONDENCE Michael P. Cancro: cancro@ 123456mail.med.upenn.edu
                Article
                Publisher ID: 20130505
                DOI: 10.1084/jem.20130505
                PMC ID: 3892970
                PubMed ID: 24367004
                SO-VID: 44e30182-bc49-49cf-9688-dcf727214fa4
                Copyright © © 2014 Goenka et al.
                License:

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                Date received : 11 March 2013
                Date accepted : 26 November 2013
                Categories
                Subject: Article

                ScienceOpen disciplines: Medicine
                Data availability:
                ScienceOpen disciplines: Medicine

                Comments

                Comment on this article

                scite_

                Similar content32

                See all similar

                Cited by47

                See all cited by

                Most referenced authors1,039

                See all reference authors